Acetic Acid → HCID 71009123, compound

HRID 1626101Notes

Reaction equation

HRID 1626101 reaction equation
C([O:3][C:4](=O)[C:5]([F:28])([F:27])[C@@:6]([C:15]1[CH:16]=[N:17][N:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Br:26])[CH:21]=2)[CH:19]=1)([NH:8][S@@:9]([C:11]([CH3:14])([CH3:13])[CH3:12])=[O:10])[CH3:7])C.[BH4-].[Li+].C(O)(=O)C.O>O1CCCC1>[Br:26][C:22]1[CH:21]=[C:20]([N:18]2[CH:19]=[C:15]([C@:6]([NH:8][S@@:9]([C:11]([CH3:14])([CH3:13])[CH3:12])=[O:10])([CH3:7])[C:5]([F:28])([F:27])[CH2:4][OH:3])[CH:16]=[N:17]2)[CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 4148881Lithium borohydrideHCID 71009060HCID 71009060, compound

Product 1

HCID 71009123HCID 71009123, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (R)-3-[1-(3-bromo-phenyl)-1H-pyrazol-4-yl]-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl ester (700 mg, 2.42 mmol) in tetrahydrofuran (5 ml) was treated slowly with lithium borohydride (2M solution in tetrahydrofuran, 0.78 ml, 2.66 mmol) at 0° C., and the mixture was stirred at 25° C. for 2 hours. For the workup, acetic acid (0.26 ml, 4.5 mmol) was added slowly over a period of 15 minutes followed by water (2 ml), and the mixture was stirred for 30 minutes at 25° C. before it was quenched with a solution of sodium hydrogencarbonate (20 ml) and extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with brine (75 ml), dried over sodium sulphate, and evaporated at reduced pressure. The crude material thus obtained was purified by column chromatography on silica gel using a gradient of hexane/ethyl acetate=85:15 to 80:20 as the eluent to give the (R)-2-methyl-propane-2-sulfinic {(R)-1-[1-(3-bromo-phenyl)-1H-pyrazol-4-yl]-2,2-difluoro-3-hydroxy-1-methyl-propyl}-amide (460 mg, 67% yield) as a deep brown solid. MS (ISP): m/z=450.2 [M+H]+.

Workup

  1. stirringthe mixture was stirred for 30 minutes at 25° C. before it
  2. customwas quenched with a solution of sodium hydrogencarbonate (20 ml)
  3. extractionextracted with ethyl acetate (3×100 ml)
  4. washThe combined organic layers were washed with brine (75 ml)
  5. dry with materialdried over sodium sulphate
  6. customevaporated at reduced pressure
  7. customThe crude material thus obtained
  8. customwas purified by column chromatography on silica gel using a gradient of hexane/ethyl acetate=85:15 to 80:20 as the eluent

Sources & evidence

ORD record
ord-1d0e507640d24bd9b507f3cf1331dd71
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

Loading…